Executive function performance in middle-aged adults

ABSTRACT. Executive functions have been widely studied in the extreme of ages, but studies in middle-aged adults remain largely neglected. Education and gender are known to influence cognitive performance; however, their effect on executive function in middle-aged adults remains unclear. Objective: The study aimed to observe the effect of hierarchy of educational qualifications (graduate, postgraduate, and PhD) and gender on various executive function tests across middle-aged adults with or without comorbidity. Methods: A total of 66 middle-aged individuals volunteered for the study (mean age=48.45±5.45 years; 20 graduates, 28 postgraduates, and 18 PhD; 36 males and 30 females; 38 healthy adults and 28 adults with comorbidities). Each subject performed a test assessing short-term memory, spatial working memory, and multitasking abilities on the Cambridge Neuropsychological Test Automated Battery with rest periods in no specific order of tests. Key parameters of cognitive tests were analyzed for differences in educational qualifications (ANOVA), gender (t-test), and the effect of comorbidity as a covariate (ANCOVA). Results: PhDs performed significantly better (p<0.05) in multitasking than graduates and had superior visuospatial working memory (fewer errors). Differences in simultaneous matching abilities, lower incongruence cost and multitasking cost were statistically significant in healthy females than in males. Conclusion: On considering adults with comorbidity, those with higher educational attainment retained the ability to multitask compared to their healthy counterparts, which was not seen in the group with lower educational attainment. Thus, higher educational attainment attenuated the influence of comorbidities and deterioration of executive functions in general in middle-aged adults.


INTRODUCTION
E xecutive function (EF) is a hypernym for the complex cognitive processes that underlie flexible, goal-directed behavioral responses to novel or difficult situations. There is a general consensus that there are three core EFs or subdomains, namely, inhibition, working memory (WM), and cognitive flexibility 1 . These higher order EFs contribute to reasoning, problem-solving, and planning 2,3 . Short-term memory also plays a significant role in contributing to executive functioning 4 .
The majority of studies have examined binary young/old adult age groups, and just a few studies have looked into age-related changes in EF in middle-aged adults or adolescents 5 . Ferguson et al. 6 suggested that middle-aged population is largely overlooked and highlighted the need of including them to provide a comprehensive life span description of the distinct developmental trajectories of EFs.
Previous studies have suggested that education influences cognitive functioning. Lower educational attainment is associated with poorer cognitive functioning in middle-aged 7 and older adults 8,9 . However, findings regarding cognitive change are mixed 10 . The role of educational attainment as a factor in contributing to the cognitive performance specific to middle-aged adults remains elusive.
Gender variations in connection to cognitive aging have also been investigated. Hughes et al. 7 suggested that in middle-aged adults, women outperform men on episodic memory tasks including immediate and delayed word recall. Middle-aged men outperform women on specific memory tests, particularly those with an analytic or spatial component 11,12 . The subject of whether men and women have different change trajectories throughout midlife and beyond is still a topic of debate.
The present research was planned in an attempt to gain insight into the cognitive performance of middle-aged adults, mainly EF. We employed the Cambridge Neuropsychological Test Automated Battery (CANTAB) computerized test batteries to assess EF performance [13][14][15] in our research. The first objective of our study was to observe the effect of educational qualification and gender on various tests of CANTAB challenging the short-term memory (DMS), visuospatial working memory (VSWM), and multitasking (MTT) in middle-aged adults, that is, between the ages of 40 and 60 years, according to the American Psychological Association 16,17 . The participants were classified on the basis of their educational qualifications, namely, graduate (G), postgraduate (PG), and doctorate of philosophy (PhD) groups. For the study to be representative of a true cross section of the middle-aged population, we did not exclude subjects on account of any comorbid condition they may have. Instead, we chose to analyze and compare the comorbid group with individuals without comorbidity, considering it as our second objective. Based on the existing literature, it was hypothesized that a higher educational qualification that is PhD will contribute to better accuracy in cognitive scores DMS, SWM, and MTT in comparison to a lower educational qualification that is G; however, reaction latencies may not be influenced. Second, gender differences would be evident in cognitive scores with females having better scores on DMS in comparison to males since females have better short-term memory 7 . Third, males will have better scores (fewer errors) in SWM task 18,19 . Fourth, individuals with comorbidities will perform worse than healthy individuals on EF tasks 20 .

METHODS
Middle-aged participants working/living on the university campus were asked to volunteer for the study via advertisements put up on notice boards in the administrative and academic blocks. The inclusion criteria of the study were as follows: • Participants within the age range of 40-60 years; • Participants who had completed formal education up to class 12; and • Participants who were able to understand English language.
Participants who scored above 26 in the Mini-Mental State Examination 21 , a scale for intact cognitive function, met the inclusion criteria for the study. In all, 66 middle-aged adults employed at the Guru Nanak Dev University in various teaching and non-teaching positions were recruited. The following information was gathered on their educational qualification.
• Those who had completed any undergraduate course after 3 years of study were regarded as graduates (G=20). • A postgraduate was someone who had completed a 2-year degree, following an undergraduate course (PG=28). • A PhD was someone who has completed doctoral level coursework (PhD=18).
Self-reported sleeping hours for the night before testing were documented. The experiment was approved by the university ethics committee and complied with the ethical standards as laid down in the Declaration of Helsinki. Participants read and signed an informed consent statement before the beginning of the experimental session.
Cambridge Neuropsychological Test Automated Battery (CANTAB) All participants were seated at a comfortable height and handed the CANTAB I-pad 22 to carry out the EF test by placing responses on a touch screen. Each test began with practice items at a basic level.

Delayed matching of sample
This level assessed both simultaneous and short-term visual memory. Participants were shown a figure composed of different colors and abstract patterns. In a four-choice recognition test of abstract patterns that share color or pattern with distracters, they were asked to choose the correct response simultaneously or after the figure got covered up and options appeared either immediately or after 4 or 12 s.

Spatial working memory
This is a self-ordered search test assessing nonverbal WM. Participants were asked to search through several colored boxes presented on the screen to find yellow tokens hidden inside. Each box contains only one token per trial. With each stage, the number of colored boxes kept on increasing.

Multitasking
This test measures the participant's ability to use multiple sources of potentially conflicting information to guide behavior and to ignore task-irrelevant information, posing a Stroop-like effect. During the test, an arrow appeared on either side of the screen or pointed in both directions. Before each trial, a cue was displayed at the top of the screen to indicate to the participant whether they must push the right or the left button, considering the cue to identify the side or the direction of the arrow. The initial part of the tests included sections during which the rule is consistent across trials that are either side of arrow or direction of the arrow (single task), and during the latter part of the sections of the test, the rule may randomly change from trial to trial (MTT).

Procedure
The demographic information of each participant was gathered. Self-reported presence of comorbidity was noted. In all, 6 people had diabetes, 8 participants had hypothyroidism, and 13 participants had hypertension. Each EF task began with a familiarization session for all participants. They were given vocal instructions with visual graphics, and then each activity had a demonstration built in before it was started. To prevent any bias in test results, the cognitive task's order was kept random (Table 1).

Statistical analysis
A priori power analysis was conducted before the study (G*power), which estimated that the minimal sample size needed was 66 participants (effect size=0.4, err prob=0.05, power 1-β err prob=0.8). A total of 68 subjects were recruited for the study; however, two subjects did not complete all the required tests, and we completed the study with 66 subjects. Statistical analysis was done using the IBM SPSS version 23 (IBM, USA) software. The statistical significance level was set at p<0.05. Since our sample population consisted of 28 comorbid individuals out of 66 individuals, analysis was done in the whole group (healthy=38, with comorbidity=28) and separately on healthy individuals. A one-way analysis of variance (ANOVA) test was applied based on their educational qualifications (G=20, PG=28, PhD=18) to the whole group and subgroups of healthy individuals and comorbid individuals. Both group-wise comparisons were made between key outcome measures of DMS, SWM, and MTT according to gender, as well as gender differences in the healthy population (males=24; females=14) that were analyzed using an independent t-test. Since approximately 41% of the participants were having some comorbidities, we decided to examine the presence of comorbidity as a covariate. An analysis of covariance (ANCOVA) was also applied to keep the presence of comorbidity as a covariate, across subgroups of educational qualifications.

RESULTS
A total of 66 middle-aged individuals (mean age=48.45±5.45 years, 20 G, 28 PG, and 18 PhD) were included in the study.
Changes in executive function scores according to education qualification ANOVA was applied on the basis of level of education.
Since values of reaction latencies and MTT correct scores were found to be heterogeneous and unequal variances were found; Welch p-values and Brown-Forsythe values were considered instead of F-values. On analyzing MTT parameters, MTT correct scores were significantly higher at F=7.73, df (2, 65), and p<0.001 in PhDs in comparison to G ( Table 2).  Similarly, group-wise comparisons according to their educational classification were made on groups of healthy individuals and comorbid individuals represented graphically (Figures 1-4). On comparison of means in the healthy group classified on the basis of educational level, the SWM total errors and between errors had a statistical significance at F=4.31, df (2, 37), p<0.05, and F=4.48, df (2, 37), p<0.05 levels, respectively, where both these variables were gradually turned down with the increase in educational qualification. Among all MTT variables, the correct score only showed significant changes with higher educational qualification, F=4.58, df (2, 37), p<0.05. The post hoc test revealed that PhD and PG groups have significantly higher MTT correct values than graduate degree holders (p<0.05).

Changes in executive function scores according to gender
On analyzing the whole group, since unequal samples were compared between males (n=36) and females (n=30), p-value with assumed unequal variances was taken into consideration. Results of the independent t-test inferred that DMS total correct scores were marginally higher in females than males. Reaction latency in a simultaneous task (overt condition) was statistically significantly lower in females (t=2.4; p<0.05) compared to males (Table 3 and 4).
Effect of level of education on executive function scores keeping presence of co morbidity as a covariate ANCOVA was applied to see the effect of level of education on EF scores with the presence of comorbidity as a covariate. MTT correct score was found to be significantly higher in adults with a PhD degree despite the presence of comorbidity in comparison to adults with graduate degrees and comorbidity, at F=5.58, df (3, 62), p<0.05.

DISCUSSION
Our study aimed to explore the effect of gender and educational qualification on EF scores of middle-aged adults with or without comorbidity. Our hypothesis that males and females would fair differently in various EF tasks challenging various subdomains of EF was proved. Another hypothesis that adults with higher educational qualification would perform better in EF tests than those with lower educational qualification was confirmed through our results similar to previous literature 10, 23 . Since individuals with comorbidity were also included in the sample population, EF scores were compared in all samples (healthy subjects+subjects with comorbidity) and the subpopulation of healthy samples for gender differences and the influence of education. It is interesting to note that in our study, the PhD group had an equal number of healthy individuals with comorbidity in comparison to graduate and postgraduate groups, which had more healthy individuals than individuals with comorbidity, yet the PhD group demonstrated higher EF scores in comparison to their counterparts. Thus, it appears that an increase in years of education may have led to protection against the negative consequences of aging on cognition.
In the DMS task, those with higher educational qualification and females performed distinctively. Trends Table 3. T-test on whole group (males=36, females=30).    indicated faster processing speed and retrieval, in both visual matching abilities and visual short-term memories of information in the PhD group in comparison to the other groups. Salthouse 24 found correct scores were higher in females in comparison to males; on the contrary, reaction latencies, which indicate the speed of processing, were also lower in females in comparison to males. Voyer et al. 25 found evidence favoring object identity memory greater in females over males. Statistically significant differences were only seen in reaction latency of simultaneous tasks, which is also referred to as the overt condition. According to Mammarella et al. 26 , DMS overt condition is regarded as a better indicator of simultaneous matching abilities. Dahlberg 27 and Jordan 28 suggested that increased simultaneous matching abilities in the case of females may be accredited to human evolution, where according to hunter-gatherer gender roles, men used to hunt animals for protection and food and women used to gather the plant food that often accounted for the meal. Hence in women, a superior pattern matching ability would be of an evolutionary advantage to recognize edible, poisonous foliage, and fruit. Reaction latencies in delayed tasks indicated better retrieval of information from memory in females, which has been demonstrated in a previous study 29 . Gender differences in SWM were found to be greater in PhDs than the others and modest among gender. The performance of the task involved that the subject had to search for tokens in spatially arranged boxes, with a single token appearing in each box once and the participant had to remember the box where the token was previously found to avoid between errors. The number of boxes increased sequentially with 4, 6, 8, and 12 boxes by the end of the task. The task challenged the VSWM in the initial stages of the task; however, as the workload increased with 8 and 12 boxes in the subsequent stages, the participants had to develop a cognitive strategy to complete the task 30 . Zarantonello et al. 19 concluded that educational level had a positive effect on WM performance on both reaction times and accuracy. Our study supports this literature with the PhD group demonstrating a lower number of total errors at all levels of test difficulty including the 12 token stages which involved the application of strategy as well as VSWM for performance execution.

Cognitive scores
On comparing scores between genders in the SWM task, the mean values of total errors and between errors were almost similar, which may reflect the near-ceiling effect of the test reported previously as well 31 . However, as the task complexity increased (at the 12-token stage), the number of errors was slightly lower in males in comparison to females (in the healthy+with comorbidity group and healthy group). Since the SWM task not only focuses on VSWM but also involves strategy as a key component, it is unclear if better results in men are by virtue of superior VSWM or cognitive strategy. Differentiating among these key components could be areas of further research.
Multitasking abilities were also enhanced as years of education increased, with our results demonstrating that PhDs were more receptive to addressing multiple stimuli and suppressing irrelevant stimuli in comparison to those with lower education qualification. The processing speed in MTT (indicated by MTT cost and incongruence cost) was found to be even superior in healthy adults with a higher degree in comparison to healthy adults with a lower degree. According to Tun and Lachman 32 , higher education (a college degree) was linked with significantly faster response latencies. However, when observing the whole group in our study, incongruence cost and MTT cost were lowest in graduates, although this can be attributed to speed accuracy trade-offs, indicating overall poor performance by the former group in the task.
Females were at an advantage in comparison to males in the MTT task. But males were found to have an advantage in reaction latency in comparison to females, in coherence with previous results by Der and Deary 33 . Both incongruence cost and MTT cost were found to be lower in the sample of all females (healthy+with comorbidity) in comparison to all males (healthy+ with comorbidity). However, the trends were found to be statistically significant (p<0.05) when only healthy women (n=14) and healthy men (n=24) were compared, excluding individuals with comorbidity, indicating clearly that females have superior MTT and cognitive inhibition and that having comorbid conditions may have compromised these abilities.
The graduate and postgraduate groups had a higher number of healthy individuals than the PhD group, which had an equal number of healthy and comorbid individuals. It is interesting to note that the PhD group had superior scores in 12 out of the total 16 key parameters assessed by CANTAB. These results reinforce the theory of cognitive reserve. Cognitive reserve is the ability to optimize or maximize performance through differential recruitment of brain networks, which perhaps reflect the use of alternate cognitive strategies 34 . Individuals with higher degrees may have performed well since education seems to boost abstract thinking abilities, allowing individuals to tackle more complicated problems 35 and achieve higher scores in EF tasks. In addition, such individuals have demanding occupational requirements requiring higher-order thinking on a daily basis.
The effect of level of education keeping the presence of comorbidity as a covariate was also investigated. A distinct finding here highlighted that MTT was significantly improved in individuals with higher educational qualification even in the presence of comorbidity in comparison to their counterparts with lower educational qualification. It is well established that cognitive performance is hampered in hypothyroidism [36][37][38][39] , hypertension 40 , and diabetes 41 , and cognitive decrement may start early in an individual with these comorbidities in comparison to controls. Educational attainment, a proxy measure for cognitive reserve, may be responsible for actively resisting the changes brought about by age and disease 42,43 . This may have ensured a better score in the EF task despite the presence of comorbidity in individuals with PhD in the present study. Our results may have broader implications for separate studies on each comorbid condition, i.e., hypothyroidism, diabetes, and hypertension to confirm the present findings of education offsetting the changes in cognition due to the aforementioned comorbidities.
Since our study was delimited to an educated working population, it was assumed that the participants met average IQ requirements. However, the fact that we did not actually measure their IQ could be considered a limitation of this study. Another limitation is the small sample size of the study.
Despite this limitation, our study provides clear evidence for greater cognitive reserve and perhaps plasticity in middle age across conditions that could potentially influence EF, with more years invested in education influencing task performances.
Among middle-aged adults, better educational attainment reduced the impact of comorbidities and the general decline in executive functions.

ACKNOWLEDGMENTS
The funding for the study came from the MYAS, GOI's NCSSR program. We also like to express our gratitude to the volunteers who agreed to participate in our study.